Immunoreactivity For Cytokeratin Research Articles

Phakomatous choristoma of the eyelid: Immunohistochemical observation

This article reports the first case of phakomatous choristoma of the eyelid in Japan. The tumor occurred in a 2-week-old boy and was located in the left lower lid near the inner canthus. An immunohistochemical study of this rare, congenital tumor was performed. The immunohistochemical analysis revealed that the epithelial cells of this tumor showed positive staining for vimentin, S-100 protein, and neuron-specific enolase, while they had no immunoreactivity for cytokeratin, glial fibrillary acidic protein, epithelial membrane antigen, or a macrophage marker. Both the epithelial cells and the central contents of the islands in this tumor showed positive staining with anti-human alpha crystallin monoclonal mouse IgG. These results strongly indicated that a phakomatous choristoma was of a lenticular origin.

The cytoskeletal intermediate filaments of canine retinal pigment epithelial cells in vivo and in vitro

The cytoskeletal intermediate filament characteristics of normal, freshly isolated and subcultured canine retinal pigment epithelial ( rpe) cells were studied using immunocytochemistry and immunoblotting techniques. Commercially available primary antibodies recognising a broad range of cytokeratins and vimentin were selected. Cytokeratin reactivity was a constant feature of all canine rpe cells. The main cytokeratins expressed by cultured RPE cells included 8, 18 and 19. This finding is consistent with the published findings of work carried out in other mammalian species including man. Freshly isolated rpe cells stained positively with broad-spectrum antibodies to cytokeratins but generally did not stain with antibodies specific to cytokeratins 18 or 19 and did not stain with antibodies to vimentin, or stained only very weakly. After a short time in culture however, cells demonstrated intense positive staining for vimentin. This study demonstrated that cytokeratin immunoreactivity (in conjunction with vimentin immunoreactivity in vitro) is a useful and consistent marker for canine RPE cells.

Contribution of the primitive epicardium to the subepicardial mesenchyme in hamster and chick embryos.

A study about the hypothetical contribution of the epicardial cells to the subepicardial mesenchyme was carried out in Syrian hamster embryos of 9-12 days post coitum (dpc) and chick embryos of 3-5 days of incubation. In the epicardium and subepicardium of these embryos we have immunolocated the proteins cytokeratin (CK), vimentin (VIM), fibronectin (FN), and two antigens related to the transformation of endocardial cells into valvuloseptal mesenchyme, ES/130 and JB3. In the hamster embryos, CK+ subepicardial mesenchymal cells (SEMC) were apparently migrating from the primitive epicardium from 9.5 dpc at the atrioventricular (AV) groove and proximal outflow tract (OFT). The morphological signs of delamination extended by 11 dpc to the epicardium of the interventricular groove and the dorsal part of the ventricle. The relative abundance of the CK+ SEMC decreased in embryos of 12 dpc. VIM colocalized with CK in most SEMC, and in some epicardial mesothelial cells, mainly at the areas of delamination. CK immunoreactivity was also found in some early subepicardial capillaries. Similar observations were made in the chick embryos studied. The immunoreactive patterns obtained at the subepicardium with anti-FN, ES/130, and JB3 antibodies were similar to those reported in the areas of endothelial transformation of the endocardial cushions. We suggest that these observations are compatible with an epithelial-mesenchymal transformation involving the epicardial mesothelium and originating at least a part of the SEMC.

O-11-152 - Craniopharyngioma: The Mayo experience with 121 cases

Craniopharyngioma is a rare, benign epithelial brain tumor of the suprasellar region with a high rate of recurrence. Clinical and histopathological features that might be predictors of recurrence/regrowth have not been clearly delineated.We compared recurrence/regrowth of the tumors with the clinico-pathological characteristics, vascular density, cell proliferation index, and immunohistochemical profile (cytokeratins, epithelial membrane antigen [EMA], carcinoembrionary antigen [CEA], and laminin) of 47 patients with craniopharyngioma followed for more than 5 years.Tumors were adamantinomatous in 42 cases (89%) and papillary squamous in 5 cases (11%). Immunoreactivity for cytokeratin 8/18/19 was positive in 64%; cytokeratin 5 in 42%; laminin 8 in 62%; and CEA in 21%. The cell proliferation index and vascular density were greater in adamantinomatous than in papillary tumors (22 ± 6 versus 17 ± 3, p = 0.05; and 21 ± 3 versus 17 ± 3, p = 0.037, respectively); they were neither related to recurrence nor to regrowth. No significant differences were found between adamantinomatous and papillary tumors regarding the presence of cytokeratin, laminin, CEA or glial fibrillary acidic protein (GFAP). Recurrence rate at 5 years was 59%. No relation was found between recurrence and adjuvant radiotherapy (AR). Residual tumor after surgery, whorl-like arrays (p = 0.04) and immunoreactivity for p53 (p = 0.022) were significantly related to recurrence/regrowth.Residual tumor after surgery, immunoreactivity to p53 and presence of whorl-like arrays are associated to recurrence/regrowth of craniopharyngioma.

Oncocytic Pheochromocytoma with Cytokeratin Reactivity

A large hemorrhagic pheochromocytoma (275 g) is described in a 38-year-old obese woman who had no history of sustained or sporadic hypertension. The tumor was unusual histologically because of the striking presence of oncocytic cells. Immunohistochemical studies revealed the positivity for neuron-specific enolase, synaptophysin, and cytokeratin CAM 5.2. Electron microscopy demonstrated neurosecretory dense core granules characteristic of a pheochromocytoma. Oncocytic pheochromocytoma was briefly documented in previous case reports but has not been well recognized. The expression of cytokeratin by pheochromocytoma is also very rare and has been described in a single study in the literature. This case had both unusual clinical and pathologic manifestations and is the first report of a pheochromocytoma with coexistence of oncocytic changes and cytokeratin immunoreactivity.

Basaloid squamous cell carcinoma of the maxilla

The study reports the first case of basaloid squamous cell carcinoma (BSCC) involving both the oral mucosa and the tuberosity area of the maxilla. The tumour showed many histological similarities to cases previously reported, though mitoses were not frequent. The immunoreactivity for cytokeratin, S-100, vimentin, Ki-67, p53, c-erbB-2 and bcl-2 was also investigated. Immunostaining for the bcl-2 protein showed a high extent of positive cells, although only a moderate staining intensity. Staining for c-erbB-2 was negative. The pathological findings and the immunoreactivity may indicate that BSCC is not as high a grade carcinoma as previously suggested. Additional studies are thus clearly needed to confirm or reject this impression.

Pattern of expression of intermediate cytokeratin filaments in the thyroid gland: an immunohistochemical study of simple and stratified epithelial-type cytokeratins.

The expression of simple and stratified epithelial-type cytokeratin (CK) intermediate filaments was evaluated by immunohistochemistry in a series of 41 papillary carcinomas, 10 follicular carcinomas, 2 poorly differentiated carcinomas and 34 specimens of normal thyroid parenchyma and lymphocytic thyroiditis. The aim of the study was to establish the CK profile of normal thyroid and thyroid carcinomas in order to clarify the putative application of CK immunostaining in diagnostic surgical pathology, and to evaluate whether the process of neoplastic transformation and tumour progression in the thyroid may be associated with any particular change in CK expression. Normal thyroid strongly expressed simple epithelial-type CKs 7 and 18 and, to a lesser degree, CKs 8 and 19, but did not express stratified epithelial-type CKs. The same pattern was found in lymphocytic thyroiditis, though the CK 19 immunoreactivity was stronger in these lesions than in the normal thyroid. Papillary and follicular thyroid carcinomas shared the expression of simple epithelial-type CKs 7, 8, 18 and 19. Immunoreactivity for CK 19 was frequently stronger and more widely distributed within each particular tumour in papillary than in follicular carcinomas, but it could also be detected, at least focally, in every follicular carcinoma. Strong expression of CK 19 highlighted small foci of papillary carcinoma not easily identifiable by conventional histological examination. Stratified epithelial-type CKs 5/6 and 13 were detected in a high percentage of papillary carcinomas, in contrast to their absence in follicular carcinomas and normal thyroid. The CK pattern was similar in primary and metastatic papillary carcinomas. We conclude that papillary carcinoma of the thyroid presents a distinct CK profile that may be used for diagnostic purposes.

Effusion cytology of malignant melanoma

Malignant effusions are complications of metastatic malignant melanoma (MM). Differential diagnosis often involves distinguishing MM from adenocarcinoma and reactive mesothelial cells. Descriptions in the literature of the morphologic and immunocytochemical (IM) staining characteristics of MM in effusions are sparse. A combination of morphology and immunocytochemistry should yield the most accurate diagnostic results. The MART-1 antigen, a transmembrane protein, is specifically expressed in melanocytes and MM. A recently developed monoclonal antibody to the MART-1 antigen may represent a useful marker for the identification of MM in effusions. The authors conducted a retrospective review of 32 effusion samples diagnosed as MM. The review consisted of morphologic and IM analyses of the effusion samples with antibodies to MART 1, HMB45, S-100, and cytokeratins (AE1/ AE3). IM stains were performed on cell block or cytospin material, depending on availability. In the morphologic review, emphasis was placed on Diff Quik-stained material, due to its enhanced cytoplasmic volume and detail. Predominant cytologic features noted were lack of cellular cohesion (in 100% of cases), large eccentric nuclei with prominent nucleoli (in 100%), multinucleation (in 84%), variable cytoplasmic vacuolization (in 75%), pigment (in 72%), and cell-in-cell engulfment (in 47%). All immunoreactive cases with sufficient material stained with at least one of the markers used. Tumor cells were positive with IM stains to MART-1 in 78% of cases, HMB45 in 81%, and S-100 in 81%. Coexpression of MART-1, HMB45, and S-100 was noted in 63% of cases. Of cases that showed expression for only 1 of the 3 antigens, the MART-1 was positive in 1 case, and HMB45 and S-100 were positive in 2 cases each. Three cases showed immunoreactivity for cytokeratins in the melanoma cells. The diagnosis of MM in effusions can be made reliably through a combination of morphologic and IM features. Differential diagnosis often involves distinguishing MM from adenocarcinoma or reactive mesothelial cells. Cytoplasmic vacuolization, multinucleation, prominent nucleoli, and cell-in-cell engulfment are cytologic features common to all three. The lack of IM staining for cytokeratins alone cannot reliably distinguish MM; 11% of cases showed positive staining with this antibody in the melanoma cells. The use of a panel of antibodies increases the accuracy of diagnosing MM. In this study, MART-1 proved a useful adjunct to the HMB45/S-100/cytokeratin panel for the diagnosis of MM in effusions, staining 78% of the immunoreactive cases, with positivity in 1 case that was negative for HMB45 and S-100.

Sarcomatoid carcinoma of the ampulla of Vater

Sarcomatoid carcinomas (carcinosarcomas) are rare lesions in the gastrointestinal tract, where they are most commonly found in the esophagus. We present the first reported case of a sarcomatoid carcinoma of the ampulla of Vater. The tumor was composed of intermixed carcinomatous (adenocarcinoma plus squamous cell carcinoma) and sarcomatous elements. Cytokeratin immunoreactivity was demonstrated focally in the sarcomatoid component, although in other areas there was positive staining for desmin and smooth muscle actin. The possible histogenesis of such lesions is briefly discussed.

Immunohistochemical evidence supporting the appendiceal origin of pseudomyxoma peritonei in women.

Women with pseudomyxoma peritonei (PMP), characterized by multifocal mucinous implants (disseminated peritoneal adenomucinosis), often have synchronous appendiceal and ovarian mucinous tumors. There has been considerable debate as to whether the ovarian tumors are secondary to the appendiceal tumor or are independent primary ovarian tumors; the latter are usually classified as mucinous tumors of low malignant potential (MLMP). It has been reported that cytokeratins (CK) 7, 18, and 20, carcinoembryonic antigen (CEA), and human alveolar macrophage 56 (HAM-56) are useful markers for distinguishing primary ovarian neoplasms from metastases of intestinal origin. Nearly all primary ovarian MLMP tumors and mucinous carcinomas are positive for CK 7, 18, and 20, CEA, and HAM-56, whereas most colorectal adenocarcinomas are negative for both CK 7 and HAM-56 and positive for CK 20 and CEA. Thirteen appendiceal and 14 ovarian mucinous tumors from 14 cases of PMP and 11 primary ovarian MLMP tumors were studied immunohistochemically for expression of CK 7, 18, and 20, monoclonal and polyclonal CEA (mCEA and pCEA), and HAM-56. Of 14 cases of PMP, 10 (71.4%) had identical staining patterns for all antibodies in both the appendiceal and ovarian tumors. For eight of these, the pattern of immunoreactivity was characterized by negative reactions for CK 7 and HAM-56 and positive reactions for CK 18 and 20, mCEA, and pCEA. One additional case for which only the ovarian tumor could be stained had the same pattern. The remaining two cases were also positive for CK 18 and 20 and CEA, but in addition were positive for CK 7. Two cases were discordant only for CK 7 and one case was discordant for both CK 7 and HAM-56. All 11 MLMP tumors were positive for CK 7 and 18, and pCEA. Eight (72.7%) of 11 were positive for HAM-56, mCEA, and CK 20. There was a statistically significant difference in the frequency of immunoreactivity for CK 7 (p = 0.0005) and HAM-56 (p = 0.0002) between the ovarian mucinous tumors in PMP and the MLMP tumors, with the ovarian tumors in PMP tending to be negative for CK 7 and HAM-56, similar to the appendiceal adenomas. Most ovarian mucinous tumors in PMP demonstrate a pattern of immunoreactivity with CK 7, 18, and 20, CEA, and HAM-56 that is identical to the associated appendiceal adenoma and distinct from primary ovarian MLMP tumors, consistent with the interpretation that these ovarian tumors are secondary to the appendiceal tumor.

Increased expression of cytokeratins 14, 18 and 19 correlates with tumor progression in the uterine cervix.

The expression of cytokeratins (CKs) in normal cervical epithelium, low grade squamous intraepithelial lesions (SIL), high grade SILs and squamous cell carcinoma (SCC) were analyzed using four different monoclonal antikeratin antibodies. In normal cervical epithelium, CK 18 showed strong immunoreactivity in basal and parabasal layers. CK 19 and 14 were expressed only in the basal layer while CK 13 was found selectively n the spinal cells. As the lesions progressed from low grade SIL to high grade SIL, immunoreactivity of CK 18, 19 and 14 in the basal cell compartment increased while the expression of CK 13 decreased. In SCC, as well-differentiated tumors showed decreased immunoreactivity for CK 18, 19 and 14 with CK 13 showing a strong and focal (localized) immunoreactivity. Undifferentiated carcinomas totally lacked CK 13 reactivity. Our findings therefore suggest that expression of CK 18, 19 and 14 may be directly related to tumor grade and CK 13 may be a marker of differentiation in cervical lesions.

Age-related changes in the medullary reticular epithelial cells of the pigeon bursa of Fabricius.

The medulla of the avian bursal lymphoid follicles contains heterogeneous cell populations, including the so-called medullary reticular epithelial cells (REC). These cells may contribute to the bursal microenvironment for B-lymphocyte differentiation and maturation. The bursa of Fabricius undergoes well-characterized posthatching developmental changes, but the age-related changes of the medullary REC have not been studied. The present study approaches this topic by analyzing hallmarks of epithelial cells: the occurrence of cytokeratin-type intermediate filaments and of desmosomes and desmoplakins in pigeon medullary REC. The bursae of Fabricius of male king pigeons (Columba livia L.) Morini's strain were examined at different ages (from hatching to 120 days after hatching) by light microscopic immunohistochemistry for pan-cytokeratins and desmoplakins and by transmission electron microscopy. The area occupied by medullary cytokeratin-immunoreactive cells was evaluated with quantitative image analysis. At hatching, cytokeratin immunoreactivity was not detected in the bursal lymphoid follicles. During the posthatching growth period of the organ (7-75 days), there was a progressive and significant increase in the area occupied by cytokeratin-immunoreactive medullary REC, in the intermediate filaments filling the cytoplasm of REC, and in the number of desmosomes. Conversely, during the regressive period analyzed (90-120 days), the density of cytokeratin-positive cells progressively decreased, although they retained their ultrastructural characteristics. The evaluation of desmoplakin immunoreactivity paralleled that of cytokeratin. The present results demonstrate that the medullary REC of the pigeon bursa of Fabricius undergoes age-dependent changes parallel with that involving the whole organ. The possible contribution of medullary REC to the bursal microenvironment is discussed.

The expression of insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) genes in the human placenta and membranes: evidence for IGF-IGFBP interactions at the feto-maternal interface.

The placenta synthesizes insulin-like growth factors (IGFs) and their binding proteins (IGFBPs), which are believed to regulate its growth and development in an autocrine/paracrine manner. To delineate the cellular sites of expression of IGP and IGFBP messenger ribonucleic acids (mRNAs) in human placenta throughout pregnancy, we used in situ hybridization histochemistry with 35S-labeled IGF and IGFBP complementary RNA probes on human placentas and fetal membranes of gestational ages 6 weeks to term (40 weeks). In placental regions where trophoblasts (fetal) or decidua (maternal) coexist (e.g. basal plate), the identity was delineated by their cytokeratin or vimentin immunoreactivity, respectively. Except for IGF-II, mRNAs encoding peptides of the IGF system were expressed in a similar spatial pattern and relative abundance throughout gestation. Both IGF mRNAs showed similar tissue distribution, but the IGF-II mRNA was more abundant than IGF-I mRNA at all gestational ages. IGF-II mRNA was expressed in the chorionic mesoderm of placental villi and chorionic plate in moderate abundance, and it decreased with gestation. It was also expressed in the trophoblasts of the cytotrophoblastic shell and Langhan's layer of placental villi only in the first trimester, suggesting an autocrine role for IGF-II in early cytotrophoblastic proliferation and/or differentiation. IGF-II mRNA was expressed most abundantly in the columns of intermediate trophoblasts in the anchoring villi and chorionic and basal plates. A gradient of IGF-II mRNA abundance was observed in the trophoblasts of the cytotrophoblastic column, with greater IGF-II mRNA levels in those at the invading front, suggesting a role for IGF-II in trophoblastic invasion. In the fetal membranes, IGF-II mRNA was identified in the amnion and chorion laeve. IGF-I receptor mRNA was expressed in low abundance in all cell types of the placenta. All six IGFBP mRNAs were identified in variable abundance in the decidualized stromal cells of the maternal decidua basalis and parietalis, with IGFBP-1 mRNA being expressed in the greatest abundance. The spatial pattern of expression of each IGFBP mRNA also differed among decidual cells, with IGFBP-1, IGFBP-2, IGFBP-4, and IGFBP-6 mRNAs being expressed in most cells, whereas IGFBP-3 and IGFBP-5 mRNAs were expressed in only some cells. IGFBP-1 mRNA was expressed initially in the epithelium of endometrial glands and in a population of decidualized stromal cells in early gestation, and subsequently in the majority of decidualized stromal cells. IGFBP-3 mRNA was expressed in both the decidua and certain intermediate trophoblasts of the basal plate and anchoring villi of placenta and in amnion and chorion laeve of fetal membranes. IGFBP-4 and IGFBP-5 mRNA were expressed additionally in low abundance in the chorionic mesoderm. IGFBP-6 was expressed in greater abundance in the decidua parietalis than in decidua basalis, although the general level of expression was low. The spatial pattern and relative abundance of expression of IGFBP mRNAs suggest IGFBP-1 to be the predominant IGFBP synthesized by the maternal decidual cells, interacting with the IGF-II that synthesizes fetal intermediate trophoblasts. Presumably, IGF-II and IGFBPs are used for cell to cell communication between fetal trophoblasts and maternal decidual cells at the feto-maternal interface for placental development and/or function.

Olfactory neuroblastoma: An immunohistochemical, ultrastructural, and flow cytometric study

CancerVolume 77, Issue 9 p. 1957-1958 CorrespondenceFree Access Olfactory neuroblastoma: An immunohistochemical, ultrastructural, and flow cytometric study Robert K. Vartanian M.D., C.M., Corresponding Author Robert K. Vartanian M.D., C.M. Vancouver Hospital & Health Sciences Center, Vancouver, B.C., CanadaVancouver Hospital & Health Sciences Center, Vancouver, B.C., Canada===Search for more papers by this author Robert K. Vartanian M.D., C.M., Corresponding Author Robert K. Vartanian M.D., C.M. Vancouver Hospital & Health Sciences Center, Vancouver, B.C., CanadaVancouver Hospital & Health Sciences Center, Vancouver, B.C., Canada===Search for more papers by this author First published: 1 May 1996 https://doi.org/10.1002/(SICI)1097-0142(19960501)77:9<1957::AID-CNCR30>3.0.CO;2-XCitations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Hirose T, Scheithauer BW, Lopes BS, Gerber HA, Altermatt HJ, Harner SG, et al. Olfactory neuroblastoma: an immunohistochemical, ultrastructural, and flow cytometric study. Cancer 1995; 76: 4– 19. 2 Franquemont DW, Fechner RE, Mills SE. Histologic classification of sinonasal intestinal-type adenocarcinoma. Am J Surg Pathol 1991; 15: 368– 75. 3 McKinney CD, Mills SE, Franquemont DW. Sinonasal intestinal-type adenocarcinoma: immunohistochemical profile and comparison with colonic adenocarcinoma. Mod Pathol 1995; 8: 421– 6. 4 Batsakis JG, Mackay B, Ordonez NG. Enteric-type adenocarcinoma of the nasal cavity. An electron microscopic and immunocytochemical study. Cancer 1984; 54: 855– 60. 5 Scopsi L, Andreola S, Pilotti S, Bufalino R, Baldini MT, Testori A, et al. Mucinous carcinoma of the breast. A clinicopathologic, histochemical, and immunocytochemical study with special reference to neuroendocrine differentiation. Am J Surg Pathol 1994; 18: 702– 11. 6 Bonkhoff H, Stein U, Remberger K. Endocrine-paracrne cell types in the prostate and prostatic adenocarcinoma are postmitotic cells. Hum Pathol 1995; 26: 167– 70. 7 Bostwick DG, Dousa MK, Crawford BG, Wollan PC. Neuroendocrine differentiation in prostatic intraepithelial neoplasia and adenocarcinoma. Am J Surg Pathol 1994; 18: 1240– 6. 8 Adlakha H, Bostwick DG. Paneth cell-like change in prostatic adenocarcinoma represents neuroendocrine differentiation: report of 30 cases. Hum Pathol 1994; 25: 135– 9. 9 Aprikian AG, Cordon-Cardo C, Fair WR, Reuter VE. Characterization of neuroendocrine differentiation in human benign prostate and prostatic adenocarcinoma. Cancer 1993; 71: 3952– 65. 10 Van de Voorde W, Poppel HV, Haustermans K, Baert I, Lauweryns J. Mucin-secreting adenocarcinoma of the prostate with neuroendocrine differentiation and paneth-like cells. Am J Surg Pathol 1994; 18: 200– 7. 11 Klimstra DS, Heffes CS, Oertel JE, Rosai J. Acinar cell carcinoma of the pancreas. A clinicopathologic study of 28 cases. Am J Surg Pathol 1992; 16: 815– 37. 12 Klimstra DS, Rosai J, Heffess CS. Mixed acinar-endocrine carcinomas of the pancreas. Am J Surg Pathol 1994; 18: 765– 78. 13 Pasquinelli G, Santini D, Preda P, Cariani G, Bonora G, Martinelli GN. Composite gastric carcinoma and precursor lesions with amphicrine features in chronic atrophic gastritis. Ultrastruct Pathol 1993; 17: 9– 24. Citing Literature Volume77, Issue91 May 1996Pages 1957-1958 ReferencesRelatedInformation

Immunohistochemical analysis of the microanatomy of primate ovary.

The ovary is a complex organ composed of cells of diverse lineages. Therefore, in this study we examined whether immunolocalization of various cytoskeletal, epithelial, immune-cell, and neural-associated proteins can differentiate various cells in the baboon and human ovaries. Surface epithelial cells exhibited immunoreactivity for cytokeratin and desmin, however, they did not immunostain for other epithelial markers such as carcinoembryonic antigen or epithelial membrane antigen. Smooth muscle actin was distributed apically whereas vimentin was localized basally in these cells. Ova exhibited strong immunoreactivity for S-100, Leu-M1, and neurofilament and did not show immunoreactivity for epithelial and cytoskeletal proteins. In antral follicles and theca cells, and after formation of corpus luteum, both granulosa and theca cells expressed immunoreactivity for vimentin. Cytokeratins were absent in the preantral and antral follicles. However, atresia and development of apoptosis was associated with expression of immunoreactive cytokeratins in atretic follicles. Development of corpus luteum led to major changes in the immunophenotype of follicular cells. The mere presence of immunoreactivity for cytokeratin and a strong immunoreactivity for desmin in the luteinized granulosa and not in the theca cells allowed discrimination of these cells from each other and from their ancestral cells. Proliferating cell nuclear antigen was present in various ovarian cells except for ovum. The distinct patterns of expression of cytoskeletal, epithelial, and neural-associated proteins in various cells of the ovary facilitates their identification and discrimination.

Cytokeratin Profiles and Mucin Secretion in Combined Hepatocellular-Cholangiocarcinoma: A Case Report

A case of a combined hepatocellular-cholangiocarcinoma (HCC-CC) is presented showing mucin production in both the HCC and the CC component. Immunohistochemical staining for cytokeratins 7 and 19 was performed and it is concluded that immunoreactivity for cytokeratin 7 and 19 is an additional criterion to the detection of mucin in making the diagnosis of a combined HCC-CC of the transitional type.

Lipid Cell (Steroid Cell) Tumor of the Ovary

Twenty-eight lipid cell (steroid cell) tumors of the ovary were studied by immunohistochemistry using an avidin-biotin complex detection system; 75% of tumors were vimentin positive, 46% were positive for cytokeratin (CAM5.2 antibody), 37% were positive with the cytokeratin cocktail AE1/AE3 and CK1, and 29% were positive for smooth muscle alpha-actin. Three tumors were positive for CD68 (KP-1), a histiocyte marker, and each of the following markers was positive in two cases: desmin, epithelial membrane antigen, neuron-specific enolase, and S-100 protein. All tumors tested were negative for chromogranin A, CD15 (Leu-M1), myoglobin, neurofilament protein, alpha-fetoprotein, carcinoembryonic antigen, and melanoma-associated antigen (HMB-45 antibody). Immunoreactivity for cytokeratins was usually focal, paranuclear, and globoid, while reactivity for actin and vimentin was diffuse and cytoplasmic. Based on these findings, melanomas and some carcinomas should be distinguishable from lipid cell tumors. However, the immunohistochemical profiles of smooth-muscle tumors, other gonadal stromal tumors (granulosa cell tumors, thecomas), and hepatocellular, renal cell, and adrenocortical carcinomas overlap with that of lipid cell tumors, and therefore these tumors may not be distinguishable from lipid cell tumors using this technique. In 10 cases (36%), negative controls exhibited weak to moderate nonspecific cytoplasmic staining. Evidence obtained using a biotin blocking kit, and a monoclonal antibody against biotin, suggests endogenous biotin-like reactivity as the source of the nonspecific staining.

Olfactory neuroblastoma. An immunohistochemical, ultrastructural, and flow cytometric study

Olfactory neuroblastoma is an uncommon neuroectodermal tumor of the upper nasal cavity, microscopic features of which are not always homogeneous. No morphologic features have been found to correlate reliably with prognosis. Twenty-six olfactory neuroblastomas occurring in 14 females and 12 males, ages 18-78 years, were studied by immunohistochemistry, electron microscopy, and DNA flow cytometry. Survival rates were statistically analyzed relative to several variables. Microscopically, 22 tumors formed a morphologic spectrum intermediate between paraganglioma (PG) and neuroblastoma (NB). Others included two ganglioneuroblastomas (GNB), one lesion exhibited biphasic (neuronal and epithelial) differentiation, and one tumor showed predominantly epithelial features. Immunoreactivity for neuronal and neuroendocrine markers included synaptophysin in 77%, neurofilament protein in 38%, class III beta-tubulin in 81%, and chromogranin A in 77%. In 88% of cases, elongated S-100 protein-positive cells surrounded tumor lobules. Cytokeratin and epithelial membrane antigen immunoreactivity were noted in six (23%) and two (8%) tumors, respectively. Aberrant p53 expression was detected in 16 tumors (62%). The Ki-67 labeling index (LI) varied from 0%-43.8% (mean, 7.4%). Ultrastructurally, 80-230 nm dense core granules were noted within perikarya and as in microtubule-containing processes in all of the 11 tumors studied by electromicroscopy. Lobules of seven tumors were surrounded by electron-dense sustentacular cells. Epithelial tumors exhibited obviously epithelial features in addition to neuronal differentiation. DNA flow cytometry demonstrated a high incidence of polyploidy and aneuploidy (78%) and a wide range of percent S phase fractions (1.5%-21.8%; mean, 9.0%). The study showed that longer survival rates are related significantly to (1) the occurrence of metastases which was linked to tumor subtype, (2) to a higher incidence of S-100 protein-positive cells, and (3) to a low (< 10%) Ki-67 labeling index. The present study indicates that (1) although typical olfactory neuroblastomas exhibit PG/NB differentiation, they more closely resemble PG, (2) occasional tumors show GNB and/or epithelial differentiation, and (3) survival rates may correlate with S-100 protein immunoreactivity and Ki-67 LI. Cancer 1995; 76:4-19.

Chondroid lipoma: An ultrastructural and immunohistochemical analysis with further observations regarding its differentiation

Chondroid lipoma was recently described as a unique, benign, pseudosarcomatous lipomatous tumor with chondroid features, often simulating liposarcoma and myxoid chondrosarcoma. An extended histochemical and immunohistochemical analysis of 13 cases, including the proliferation markers, proliferating cell nuclear antigen (PCNA) and Ki67, as well as ultrastructural studies of eight cases were performed with the intent of further elucidating its differentiation. Staining with toluidine blue and alcian blue at controlled pHs indicated the presence of chondroitin sulfates within the myxohyaline matrix. Immunohistochemically, all tumors were positive for vimentin and S100 protein. Focal immunoreactivity for cytokeratins was seen in 3 of 13 cases; one of these also had intracytoplasmic tonofilament bundles ultrastructurally. Scattered tumor cells stained for CD68 antigen with KP1 in 6 of 13 cases. None of the tumors stained for epithelial membrane antigen (EMA) or α-smooth muscle actin. Collagen IV immunostains showed a network of fibrils encircling individual tumor cells in 10 of 13 cases. Intracytoplasmic staining for laminin was found in 9 of 13 cases. Ultrastructurally there was a spectrum of differentiation, ranging from primitive cells sharing features of prelipoblasts and chondroblasts, to lipoblasts and preadipocytes, to mature adipocytes. A striking ultrastructural feature in 5 of 8 cases was the presence of knob-like protrusions of the cell membrane, which contained granular, amorphous, and fibrillar material that appeared to be extruded into the adjacent matrix. The myxohyaline matrix had ultrastructural features of cartilage. Numerous mitochondria and lysosomes were absent, indicating that chondroid lipoma is neither a hibernomatous lesion nor a lipogranuloma. Ki67 immunoreactivity was typically very low and detected only in the more primitive cell population. The findings in this analysis indicate that chondroid lipoma is a pseudosarcomatous lipogenic neoplasm with a unique cell population possessing predominantly features of embryonal fat and, to a lesser extent, embryonal cartilage.

Intermediate filaments in the testis of the teleost mosquito fish Gambusia affinis holbrooki: a light and electron microscope immunocytochemical study and Western blotting analysis

A light and electron microscope immunocytochemical study and Western blotting analysis has been performed on intermediate filaments (vimentin, desmin and cytokeratins) in the testis of the teleost fish Gambusia affinis holbrooki. An immunoreaction to vimentin was observed in the epithelium of the efferent ducts, testicular canal and their surrounding peritubular cells. Positive vimentin immunostaining was also observed in the cells located around seminiferous tubules (boundary cells), Leydig cells, interstitial fibroblasts, chromatophores, and blood vessel endothelial cells. In contrast to mammals, no vimentin immunoreactivity was found in the Sertoli cells. Immunoreactivity to desmin was weak in the epithelial cells of the efferent ducts and testicular canal and intense in the peritubular cells that surrounded these ducts. Desmin immunoreactivity was also observed in the seminiferous tubule boundary cells. The immunoreactivity was weak in the boundary cells that surrounded germ cell cysts containing spermatogonia or spermatocytes and intense in the boundary cells around cysts with elongated or mature spermatids. Immunoreactivity towards cytokeratins was observed only in testicular blood vessels. Cytokeratin immunolabelling was intense in the endothelium and weak in the vascular smooth muscle cells. No cytokeratin immunoreactivity was found in the Sertoli cells, germ cells, interstitial cells or in the efferent duct epithelium. The absence of intermediate filaments in the Sertoli cells, the absence of cytokeratins in the epithelium of the sperm excretory ducts, and the presence of desmin filaments in these epithelial cells are the most important differences with regards to the intermediate filament phenotype in mammalian testes.